Method for blood withdrawal and infusion using a pressure controller

ABSTRACT

A method and apparatus for controlling blood withdrawal and infusion flow rate with the use of a pressure controller. The pressure controller uses pressure targets based upon occlusion limits that are calculated as a function of flow. The controller has the ability to switch from controlling withdrawal pressure to controlling infusion pressure based upon the detection of an occlusion. The controller distinguishes between partial and total occlusions of the withdrawal vein providing blood access. Depending on the nature of occlusion, the controller limits or temporarily reverses blood flow and, thus, prevents withdrawal vessel collapse or reverses blood flow to quickly infuse blood into the vessel without participation from operator.

RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.12/719,667 filed Mar. 8, 2012, which is a divisional of U.S. patentapplication Ser. No. 10/601,574 (U.S. Pat. No. 7,674,237) filed Jun. 24,2003, which is a divisional of U.S. patent application Ser. No.09/703,702 (U.S. Pat. No. 6,585,675) filed Nov. 2, 2000, the entirety ofthese applications are incorporated by reference.

FIELD OF INVENTION

The invention relates to the field of pressure controllers for fluidicpumping systems and, in particular, to pressure controllers forintravenous blood pumps.

BACKGROUND OF THE INVENTION

There are a number of medical treatments, such as ultrafiltration,apheresis and dialysis, that require blood to be temporarily withdrawnfrom a patient and returned to the body shortly thereafter. While theblood is temporarily outside of the body, it flows through an“extracorporeal blood circuit” of tubes, filters, pumps and/or othermedical components. In some treatments, the blood flow is propelled bythe patient's blood pressure and gravity, and no artificial pump isrequired. In other treatments, blood pumps in the extracorporeal circuitprovide additional force to move the blood through the circuit and tocontrol the flow rate of blood through the circuit. These pumps may beperistaltic or roller pumps, which are easy to sterilize, are known tocause minimal clotting and damage to the blood cells, and areinexpensive and reliable.

Brushed and brushless DC motors are commonly used to rotate peristalticpumps. A motor controller regulates the rotational speed of blood pumps.The speed of a pump, expressed as rotations per minute (RPM), regulatesthe flow rate of the blood through the circuit. Each revolution of thepump moves a known volume of blood through the circuit. Thus, the bloodflow rate through the circuit can be easily derived from the pump speed.Accordingly, the pump speed provides a relatively accurate indicator forthe volume flow of blood through an extracorporeal circuit.

Existing pump controllers may be as simple as a potentiometer thatregulates the voltage to the pump DC motor. The pump speed isproportional to the voltage applied to the pump motor. By increasing thevoltage, the speed of the pump increases and, similarly, the blood flowincreases through the extracorporeal circuit. More sophisticatedexisting pump controllers, such as used in current dialysis machines,include a microprocessor that executes a software/firmware program toregulate the pump speed and, thus, blood flow in accordance withpump/flow settings entered by an operator. In these controllers, themicroprocessor receives input commands from an operator who selects adesired blood flow using a user interface on the controller housing. Themicroprocessor determines the pump motor speed needed to provide theselected blood flow rate, and then issues commands to the pump motor torun at the proper speed.

To improve the accuracy and reliability of the blood flow through anextracorporeal circuit, existing pump controller microprocessors receivefeedback signals from, for example, tachometers or optical encoders thatsense the actual speed of the pump motor. Similarly, feedback signalshave been provided by ultrasonic flow probes that measure the actualflow of blood in the extracorporeal circuit. By comparing the desiredpump speed or flow rate to the measured pump speed or flow rate, themicroprocessor can properly adjust the pump speed to correct for anydifference between the desired and actual speed or rate. In addition, acalculated or measured flow value (actual flow rate) may be displayed onthe pump console for viewing by the operator for a visual comparisonwith the desired flow setting.

The microprocessor controllers for blood pumps have, in the past, reliedon both open and closed loop control of the motor speed. The open loopcontrol normally consists of a constant feed forward voltage (based onthe back EMF constant of the motor). The closed loop control systems usevelocity feedback in the form of a tachometer, encoder or resolver tomaintain constant pump flow. A constant flow control loop allows a userto set the blood flow rate, and the controller regulates the pump speedto maintain a constant blood flow, unless a malfunction occurs thatwould require the pump to be shut-down to protect the patient. The openloop control systems have the disadvantage that an increase or decreasein torque or motor resistance due to temperature will result in somevariation in pump flow. This variation will generally be small when themotor is geared. Torque variations are not an issue for closed loopcontrol systems because they use the motor velocity as feedback andadjust the supply current or voltage to the motor in order to maintainconstant velocity.

Existing blood pump controllers include various alarms and interlocksthat are set by a nurse or a medical technician (collectively referredto as the operator), and are intended to protect the patient. In atypical dialysis apparatus, the blood withdrawal and blood returnpressures are measured in real time, so that sudden pressure changes arequickly detected. Sudden pressure changes in the blood circuit aretreated as indicating an occlusion or a disconnect in the circuit. Thedetection of a sudden pressure change causes the controller to stop thepump and cease withdrawal of blood. The nurse or operator sets the alarmlimits for the real time pressure measurements well beyond the expectednormal operating pressure for the selected blood flow, but within a safepressure operating range.

Examples of existing blood pump controllers are disclosed in U.S. Pat.Nos. 5,536,237 ('237 patent) and 4,657,529 ('529 patent). Thecontrollers disclosed in these patents purport to optimize the rate ofblood flow through a blood circuit based on a pressure vs. flow ratecontrol curve. However, these patents do not teach controlling a bloodpump based on control curves for both withdrawal and infusion pressures,and do not suggest reversing blood flow to relieve an occlusion. Theauthors of the '237 and '529 patents acknowledged that during bloodwithdrawal, treatment is often interrupted if the vein is collapsed.They further acknowledged that as the result of such collapse the needlecould be drawn into the blood vessel wall that makes the recoverydifficult. The remedy proposed by these authors is to always withdrawblood at a rate that prevents the collapse of the vein by applying acomplex system of identification of the vein capacity prior totreatment. The '237 patent specifically addresses the difficulty ofgenerating ad-hoc pressure flow relationships for individual patientswith low venous flow capacity. However, the experience of the presentapplicants is that the withdrawal properties of venous access in manypatients are prone to frequent and often abrupt changes duringtreatment. Accordingly, the approach advanced in the '237 and '529patents of attempting to always avoid vein collapse will fail when avein collapse condition occurs and does not provide any remedy for veincollapse (other than to terminate treatment and call a nurse or doctor).

Pressure conditions in a blood circuit often change because of bloodviscosity changes (that in turn affect flow resistance), and because ofsmall blood clots that form where blood stagnates on the surface oftubes and cannulae. These small clots partially occlude the bloodcircuit, but do not totally obstruct blood flow through the circuit.These clot restrictions increase the flow resistance and, thus, increasethe magnitude of pressure in the circuit. Accordingly, an assumptionthat the flow resistance and pressure are constants in a blood circuitmay not be valid. Gravity is another source of pressure change in ablood circuit. Gravity affects the pressure in a blood circuit. Thepressure in the circuit will change due to gravity if the patient movessuch that the height changes occur with respect to the vertical positionof the circuit entry and exit points on the patient's arms relative tothe pressure sensors. The pressure sensors in the blood circuit maydetect a change that is indicative of a change in the patient'sposition, rather than a clot in the circuit. For example, if the patientsits up, pressure sensors will detect pressure changes of the blood inthe circuit.

If the gravity induced pressure changes are sufficiently large, priorpump controllers tended to activate an alarm and shut down the bloodpump. The operator then has to respond to the alarm, analyze thesituation and remedy the malfunction or change the alarm limits if theflow path conditions have changed. In more advanced systems the operatorsets the alarm window size (for example, plus or minus 50 mmHg about amean point), and the machine will automatically adjust the mean point inproportion to the flow setting change. If the measured pressure exceedsthe pressure range set by the window, the blood flow is automaticallystopped. However, existing systems do not adjust the pump speed inresponse to changes in flow resistance, but rather, shut down if theresistance (and hence fluid pressure) become excessive.

SUMMARY OF THE INVENTION

A blood flow controller has been developed that controls blood flowthrough an extracorporeal blood circuit. The controller regulates theflow rate through the circuit such that: (a) blood is withdrawn from aperipheral vein in the patient (which veins are usually small,collapsible tubes) at a blood flow rate sustainable by the vein andwhich avoids collapsing the vein, and (b) blood pressure changes in thecircuit are compensated for by adjusting pump speed and hence the flowrate through the circuit. The controller sets a flow rate of bloodthrough the circuit based on both a maximum flow rate limit and avariable limit of pressure vs. flow rate. These limits may bepreprogrammed in the controller and/or selected by an operator.

A novel blood withdrawal system has been developed that enables rapidand safe recovery from occlusions in a withdrawal vein withoutparticipation of an operator, loss of circuits to clotting, or annoyingalarms. Applicants have developed a technique of compensating for andremedying temporary vein collapse when it occurs during bloodwithdrawal. They recognized that not all episodes of a vein collapserequire intervention from a doctor or nurse, and do not require thatblood withdrawal ceased for an extended period. For example, veincollapse can temporarily occur when the patient moves or a venous spasmcauses the vein to collapse in a manner that is too rapid to anticipateand temporary. There has been a long-felt need for a control system foran extracorporeal circuit that can automatically recover from temporaryocclusions. Applicants developed a system that temporarily stops bloodwithdrawal when vein collapse occurs and, in certain circumstances,infuses blood into the collapsed vein to reopen the collapsed vein.Applicants' approach to vein collapse is counterintuitive and contraryto the approach disclosed in the '237 and '529 patents.

Peripheral vein access presents unique problems that make it difficultfor a blood withdrawal controller to maintain constant flow and not tocreate hazards for the patient. These problems are unlike thoseencountered with conventional dialysis treatments that rely on asurgically created arterio-venous shunt or fistula to withdraw blood andare administered in controlled dialysis centers. Using the presentcontroller, for example, a patient may stand up during treatment andthereby increase the static pressure head height on the infusion sideresulting in a false occlusion. The controller adjusts the blood flowrate through the extracorporeal circuit to accommodate for pressurechanges. As the patient rises each centimeter (cm), the measuredpressure in the extracorporeal circuit may increase by 0.73 mm Hg(milliliter of mercury). A change in height of 30 cm (approximately 1ft) will result in a pressure change of 21 mm Hg. In addition, thepatient may bend his/her arm during treatment and, thereby, reduce theblood flow to the withdrawal vein. As the flow through the withdrawalcatheter decreases, the controller reduces pump speed to reduce thewithdrawal pressure level. Moreover, the blood infusion side of theblood circulation circuit may involve similar pressure variances. Theseinfusion side pressure changes are also monitored by the controllerwhich may adjust the pump to accommodate such changes.

The controller may be incorporated into a blood withdrawal and infusionpressure control system which optimizes blood flow at or below a presetrate in accordance with a controller algorithm that is determined foreach particular make or model of an extraction and infusionextracorporeal blood system. The controller is further a blood flowcontrol system that uses real time pressure as a feedback signal that isapplied to control the withdrawal and infusion pressures within flowrate and pressure limits that are determined in real time as a functionof the flow withdrawn from peripheral vein access.

The controller may govern the pump speed based on control algorithms andin response to pressure signals from pressure sensors that detectpressures in the blood flow at various locations in the extracorporealcircuit. One example of a control algorithm is a linear relationshipbetween a minimum withdrawal pressure and withdrawal blood flow. Anotherpossible control algorithm is a maximum withdrawal flow rate. Similarly,a control algorithm may be specified for the infusion pressure of theblood returned to the patient. In operation, the controller seeks amaximum blood flow rate that satisfies the control algorithms bymonitoring the blood pressure in the withdrawal tube (and optionally inthe infusion tube) of the blood circuit, and by controlling the flowrate with a variable pump speed. The controller uses the highestanticipated resistance for the circuit and therefore does not adjustflow until this resistance has been exceeded. If the maximum flow rateresults in a pressure level outside of the pressure limit for theexisting flow rate, the controller responds by reducing the flow rate,such as by reducing the speed of a roller pump, until the pressure inthe circuit is no greater than the minimum (or maximum for infusion)variable pressure limit. The controller automatically adjusts the pumpspeed to regulate the flow rate and the pressure in the circuit. In thismanner, the controller maintains the blood pressure in the circuitwithin both the flow rate limit and the variable pressure limits thathave been preprogrammed or entered in the controller.

In normal operation, the controller causes the pump to drive the bloodthrough the extracorporeal circuit at a set maximum flow rate. Inaddition, the controller monitors the pressure to ensure that itconforms to the programmed variable pressure vs. flow limit. Eachpressure vs. flow limit prescribes a minimum (or maximum) pressure inthe withdrawal tube (or infusion tube) as a function of blood flow rate.If the blood pressure falls or rises beyond the pressure limit for acurrent flow rate, the controller adjusts the blood flow by reducing thepump speed. With the reduced blood flow, the pressure should rise in thewithdrawal tube (or fall in the return infusion tube). The controllermay continue to reduce the pump speed, until the pressure conforms tothe pressure limit for the then current flow rate.

When the pressure of the adjusted blood flow, e.g. a reduced flow, is noless than (or no greater than) the pressure limit for that new flow rate(as determined by the variable pressure vs. flow condition), thecontroller maintains the pump speed and operation of the blood circuitat a constant rate. The controller may gradually advance the flow ratein response to an improved access condition, provided that the circuitremains in compliance with the maximum rate and the pressure vs. flowlimit.

The controller has several advantages over the prior art including(without limitation): that the controller adjusts the pump speed toregulate the blood flow rate and maintain the blood pressure withinprescribed limits, without requiring the attention of or adjustment byan operator; the controller adjusts blood flow in accordance with anocclusion pressure limit that varies with flow rate, and the controlleradaptively responds to partial occlusions in the withdrawal blood flow.In addition, the controller implements other safety features, such as todetect the occurrence of total unrecoverable occlusions in the circuitand disconnections of the circuit, which can cause the controller tointerpret that blood loss is occurring through the extracorporealcircuit to the external environment and stop the pump.

The controller may also compensate for variances in flow restrictionsusing control algorithms that apply two pressure targets: a withdrawalocclusion pressure target, and an infusion occlusion pressure target. Bycompensating for two control targets, the controller can monitor anddiscretely or simultaneously adjust for flow restrictions, e.g., partialocclusions, that occur in the withdrawal or infusion lines of the bloodcircuit. For example, if an occlusion occurs in the withdrawal vein, thepressure drop in the withdrawal line is sensed by the controller whichin turn reduces the flow rate in accordance with an adjustablewithdrawal pressure limit. The pump continues at a reduced speed,provided that the variable pressure vs. flow limit is satisfied and theboundary limits of the pressure vs. flow relationship are not exceeded.The controller may be required to stop the pump entirely, if the blooddoes not flow sufficiently (with acceptable pressure) at any pump speed.In such a condition, the controller will slow the pump to a stop as thewithdrawal pressure target decreases. When the flow drops below apreprogrammed limit for a preprogrammed time, the pump will also bestopped by the flow controller and the user alarm will be activated.

In the event of a withdrawal pressure occlusion that terminates flow,the flow controller will temporarily reverse the flow of the pump in anattempt to remove the withdrawal occlusion. The occlusion algorithms arestill active during this maneuver, and will also terminate flow if theocclusion cannot be removed. The volume displacement of the pump islimited to a specific number of revolutions to ensure that the pump doesnot infuse air into the patient.

With respect to the infusion pressure target, if a partial occlusionoccurs in the infusion vein, the pressure controller detects a pressurerise in the return line and reduces the infusion rate. The controllerwill continue to reduce the pump speed and reduce the pressure in theinfusion line. If the occlusion is total, the controller will quicklyreduce the pump speed to a stop and avoid excessive pressure beingapplied to the infusion vein. The controller may also activate an alarmwhenever the pump speed is stopped (or reduced to some lower speedlevel).

An application of the controller is in an extracorporeal blood systemthat includes a filter and blood pump in a blood circuit. This systemextracts excess fluid from the blood of a fluid overloaded patient. Theamount of excess fluid that is withdrawn from the blood is set by theoperator at a clinically relevant rate to relieve the overloadedcondition of the patient. The system accesses the peripheral veins ofthe patient, and avoids the need to access central venous blood. Thefilter system provides a simple method for controlling blood extractionfrom a peripheral vein. Thus, the blood filtering system could be usedin a physician's clinic and outside of an ICU (intensive care unit of ahospital).

The blood filter system may provide an acceptable level of invasiveness,e.g., minimally invasive, for a fluid removal treatment in the desiredenvironment and patient population via a peripheral vein preferably inan arm of a patient. Such access is commonly established by a nurse inorder to draw blood or to infuse drugs. The filter system may withdrawup to 80% or intermittently up to 100% of the available blood fluid flowfrom the vein without causing the vein to collapse. Because of itsreduced invasiveness, the filter system does not require an ICU or aspecial dialysis setting to be administered to a patient. If anapparatus for slow continuous ultrafiltration was available that woulddraw and re-infuse blood into the body using the access site similar toa common intravenous (IV) therapy, such a device would have a widespreadclinical use.

The controller/filter system further provides a mechanism formaintaining patient safety while preventing false alarms when bloodpressure measurements are made with or without the use of a bloodpressure cuff.

SUMMARY OF THE DRAWINGS

A preferred embodiment and best mode of the invention is illustrated inthe attached drawings that are described as follows:

FIG. 1 illustrates the treatment of a patient with an ultrafiltrationsystem using a controller in accordance with the present invention tomonitor and control pressure and flow in an extracorporeal bloodcircuit.

FIG. 2 illustrates the operation and fluid path of the blood circuitshown in FIG. 1.

FIG. 3 is a chart of the withdrawal occlusion and disconnect limitsapplied by the controller.

FIG. 4 is a flow chart of an algorithm to implement the occlusion anddisconnect limits shown in FIGS. 3 and 6, and showing how the bloodwithdrawal and infusion occlusion and disconnect pressures arecalculated as a function of measured blood flow.

FIG. 5 is a flow chart of an algorithm showing a blood withdrawal andinfusion PIFF pressure control algorithm to be implemented by thecontroller.

FIG. 6 is a chart of infusion occlusion and disconnect limits for theultrafiltration system.

FIG. 7 is a component diagram of the controller (including controllerCPU, monitoring CPU and motor CPU), and of the sensor inputs andactuator outputs that interact with the controller.

FIG. 8 is an illustration of the system response to the partialocclusion of the withdrawal vein in a patient.

FIG. 9 is an illustration of the system response to the completeocclusion and temporary collapse of the withdrawal vein in a patient.

DETAILED DESCRIPTION OF THE INVENTION

A pump controller has been developed which may be incorporated in anextracorporeal blood circuit system. This system in an exemplaryembodiment withdraws blood from a peripheral vein of a patient,processes the blood, e.g., passes the blood through a pump and filter,and returns the blood to the same or another peripheral vein. The pumpcontroller monitors the blood pressure in the blood circuit and adjuststhe speed of the pump (and hence the blood flow rate through thecircuit) to comply with multiple limits on the pressure level and flowrates in the circuit. In addition, the controller promptly reacts to anychanges in the pressure in the circuit.

The withdrawal and infusion of blood from a peripheral vein (orperipheral artery) in a mammalian patient (whether the patient is ahuman or other mammal) presents unique problems, which have beensuccessfully addressed by the controller disclosed here. A peripheralvein in a human is a hollow tube, having approximately a 2 to 4 mminternal diameter. The wall of the vein is soft, flexible and notstructurally self-supporting.

Blood pressure in the vein is required to keep the blood passage openand blood flowing through the vein. In a human vein, normal bloodpressure in a vein is between 5 and 20 mmHg (millimeters of mercury).The blood flow through a peripheral vein generally ranges between 50 and200 ml/min (milliliters per minute). Maintaining adequate pressure in ablood vessel from which blood is being withdrawn ensures that the vesselremains open to the flow of blood. The vein will collapse if thepressure drops excessively in a blood vessel, e.g., a vein. If thepressure in the vein becomes sub-atmospheric, the outside atmosphericpressure acting on the body will cause the vein to collapse.

An extracorporeal blood circuit draws blood from a peripheral vein (orartery) by applying a low pressure to a blood withdrawal tube attachedto a catheter inserted into the vein. The pressure in the withdrawaltube is lower than the blood pressure in the vein. Due to this lowpressure, some blood in the vein is drawn into the catheter andwithdrawal tube. The lower pressure in the withdrawal tube and catheteris created by a pump in the blood circuit system that draws bloodthrough the circuit and, in doing so, reduces the pressure in thewithdrawal tube that is upstream of the pump. The reduced pressure inthe withdrawal tube also reduces the pressure in the catheter and in theperipheral vein in which the catheter needle is inserted.

The reduced pressure in the vein near the catheter creates a potentialrisk of withdrawing blood from a peripheral vein too quickly andcollapsing the vein. If the rate of blood flow into the withdrawalcatheter is too great, the blood pressure in the vein will drop belowthat pressure required to keep the vein open and the vein will begin tocollapse. As the vein collapses around the catheter, the blood flow intothe catheter and the blood circuit is gradually reduced due torestrictions (“occlusions”) in the collapsing vein. As the blood flowinto the blood circuit decreases, the pressure in the withdrawal linedrops further because the pump (if it remains at a constant speed) isstill attempting to pull blood through the circuit at a constant rate.Thus, the pump can accelerate the collapse of the withdrawal vein byexacerbating the pressure drop in the vein, unless the speed of the pumpis reduced before the vein fully collapses.

The novel pressure controller disclosed here prevents complete veincollapse by reducing the blood withdrawal flow rate in response to apressure drop in a withdrawal tube. If the vein collapses neverthelessintermittently, the controller facilitates recovery and continues theblood withdrawal. A pressure sensor in the withdrawal tube monitors theblood pressure in real time. If and when a pressure drop is detectedwhich exceeds the specified allowed limit in the withdrawal line, thecontroller (which receives and processes the pressure sensor signal)slows the blood pump to reduce the flow rate of blood being withdrawnfrom the peripheral vein. By slowing the withdrawal flow, the pressurein the withdrawal line and peripheral vein near the catheter may returnto a higher level. This pressure increase will hopefully be sufficientto prevent vein collapse, before it actually occurs and allow for acontinued withdrawal blood flow (albeit at a reduced withdrawal flow).However, if the pressure in the withdrawal line does not sufficientlyelevate and the vein continues to fully collapse, the controller willdetect the continued low pressure in the withdrawal line and continue toreduce the pump flow until the pump stops.

An embodiment of the present invention is a pump controller in anintravenous blood filtering system that withdraws blood from peripheralblood vessels. The controller includes a microprocessor and memory forstoring data and software control algorithms. The microprocessorreceives input signals from pressure sensors regarding the blood andultrafiltrate pressures in the extracorporeal circuit, and from the pumpregarding the pump speed. The microprocessor processes these inputsignals, applies the control algorithms and generates control signalsthat regulate the pump and hence the flow rate of blood and/orultrafiltrate through the circuit.

The controller may regulate blood withdrawn from a peripheral vein to aflow rate in a normal range of 0 to 150 ml/min (milliliters per minute).An operator may select a maximum withdrawal flow rate within this normalpressure range at which the blood filtering system is to operate. Thecontroller will maintain the flow rate at or near the desired flow rate,provided that there is compliance with a pressure vs. flow rate limitcontrol algorithm. The controller maintains the withdrawal blood flowrate at the selected maximum flow rate, but automatically reduces theflow rate if the pressure in the system falls below a pressure limit forthe actual flow rate. Thus, if there develops a partial flow restrictionin the withdrawal vein or in the extracorporeal system, the controllerwill react by reducing the flow rate.

The controller optimizes blood flow at or below a preset maximum flowrate in accordance with one or more pressure vs. flow algorithms. Thesealgorithms may be stored in memory of the controller which includes aprocessor, e.g., microprocessor; memory for data and program storage;input/output (I/O) devices for interacting with a human operator, forreceiving feedback signals, e.g., pressure signals, from the bloodcircuit and possibly other systems, e.g., patient condition, and forissuing commands to control the pump speed; and data busses to allow thecontroller components to communicate with one another.

The control algorithms may include (without limitations): maximum flowsettings for an individual patient treatment that is entered by theoperator, a data listing of acceptable withdrawal/line pressures foreach of a series of flow rates, and mathematical equations, e.g.,linear, which correlates acceptable pressure to a flow rate. Thealgorithms may be determined for each particular make or model of anextraction and infusion extracorporeal blood system. In the presentembodiment, the pressure vs flow rate curves for occlusion anddisconnect for the specified blood circuits are preprogrammed into thesystem.

Feedback signals are also used by the controller to confirm that thecontrol algorithms are being satisfied. A real time pressure sensorsignal from the withdrawal tube may be transmitted (via wire orwireless) to the controller. This pressure signal is applied by thecontroller as a feedback signal to compare the actual pressure with thepressure limits stored in memory of the controller for the current flowrate through the blood circuit. Based on this comparison, the controllersends control commands to adjust the speed of the pump motor, whichcontrols the withdrawal and infusion pressures in the blood circuit.Using the pressure feedback signal, the controller ensures that the flowrate in the circuit complies with the variable pressure limits.Moreover, the pressure is monitored in real time every 10 ms so that thecontroller may continually determine whether the flow rate/pressure isacceptable. This is achieved by looking at the average flow rate over aconsecutive one second period, and if the flow is less than a presetrate, the pump is stopped.

The exemplary apparatus described here is an ultrafiltration apparatusdesigned for the extraction of plasma water from human blood. To extractplasma water (ultrafiltrate), the apparatus includes a filter. Thefilter has a membrane that is permeable to water and small molecules,and impermeable to blood cells, proteins and other large solutesparticles. FIG. 1 illustrates the treatment of a fluid overloadedpatient with an ultrafiltration apparatus 100. The patient 101, such asa human or other mammal, may be treated while in bed or sitting in achair and may be conscious or asleep. The apparatus may be attached tothe patient in a doctor's office, an outpatient clinic, and may even besuitable for use at home (provided that adequate supervision of a doctoror other medically trained person is present). The patient need not beconfined to an intensive care unit (ICU), does not require surgery to beattached to the ultrafiltration apparatus, and does not need specializedcare or the continual presence of medical attendants.

To initiate ultrafiltration treatment, two standard 18G (gage) catheterneedles, a withdrawal needle 102 and a infusion (return) needle 103, areintroduced into suitable peripheral veins (on the same or differentarms) for the withdrawal and return of the blood. This procedure ofinserting needles is similar to that used for inserting catheter needlesto withdraw blood or for intravenous (IV) therapy. The needles areattached to withdrawal tubing 104 and return tubing 105, respectively.The tubing may be secured to skin with adhesive tape.

The ultrafiltration apparatus includes a blood pump console 106 and ablood circuit 107. The console includes two rotating roller pumps thatmove blood and ultrafiltrate fluids through the circuit, and the circuitis mounted on the console. The blood circuit includes a continuous bloodpassage between the withdrawal catheter 102 and the return catheter 103.The blood circuit includes a blood filter 108; pressure sensors 109 (inwithdrawal tube), 110 (in return tube) and 111 (in filtrate outputtube); an ultrafiltrate collection bag 112 and tubing lines to connectthese components and form a continuous blood passage from the withdrawalto the infusion catheters an ultrafiltrate passage from the filter tothe ultrafiltrate bag. The blood passage through the circuit ispreferably continuous, smooth and free of stagnate blood pools andair/blood interfaces. These passages with continuous airless blood flowreduce the damping of pressure signals by the system and allows for ahigher frequency response pressure controller, which allows the pressurecontroller to adjust the pump velocity more quickly to changes inpressure, thereby maintaining accurate pressure control without causingoscillation. The components of the circuit may be selected to providesmooth and continuous blood passages, such as a long, slendercylindrical filter chamber, and pressure sensors having cylindrical flowpassage with electronic sensors embedded in a wall of the passage. Thecircuit may come in a sterile package and is intended that each circuitbe used for a single treatment. A more detailed description of anexemplary blood circuit is included in commonly owned and co-pendingU.S. Pat. No. 6,887,214 (U.S. patent application Ser. No. 09/660,195,filed Sep. 12, 2000), which is incorporated by reference.

The circuit mounts on the blood and ultrafiltrate pumps 113 (for bloodpassage) and 114 (for filtrate output of filter). The circuit can bemounted, primed and prepared for operation within minutes by oneoperator. The operator of the blood ultrafiltration apparatus 100, e.g.,a nurse or medical technician, sets the maximum rate at which fluid isto be removed from the blood of the patient. These settings are enteredinto the blood pump console 106 using the user interface, which mayinclude a display 115 and control panel 116 with control keys forentering maximum flow rate and other controller settings. Information toassist the user in priming, setup and operation is displayed on the LCD(liquid crystal display) 115.

The ultrafiltrate is withdrawn by the ultrafiltrate pump 114 into agraduated collection bag 112. When the bag is full, ultrafiltrationstops until the bag is emptied. The controller may determine when thebag is filled by determining the amount of filtrate entering the bagbased on the volume displacement of the ultrafiltrate pump in thefiltrate line and filtrate pump speed, or by receiving a signalindicative of the weight of the collection bag. As the blood is pumpedthrough the circuit, an air detector 117 monitors for the presence ofair in the blood circuit. A blood leak detector 118 in the ultrafiltrateoutput monitors for the presence of a ruptured filter. Signals from theair detector and/or blood leak detector may be transmitted to thecontroller, which in turn issues an alarm if a blood leak or air isdetected in the ultrafiltrate or blood tubing passages of theextracorporeal circuit.

FIG. 2 illustrates the operation and fluid paths of blood andultrafiltrate through the blood circuit 107. Blood is withdrawn from thepatient through an 18 Gage or similar withdrawal needle 102. Thewithdrawal needle 102 is inserted into a suitable peripheral vein in thepatient's arm. The blood flow from the peripheral vein into thewithdrawal tubing 104 is dependent on the fluid pressure in that tubingwhich is controlled by a roller pump 113 on the console 106.

The length of withdrawal tubing between the withdrawal catheter and pump113 may be approximately two meters. The withdrawal tubing and the othertubing in the blood circuit may be formed of medical PVC (polyvinylchloride) of the kind typically used for IV (intravenous) lines whichgenerally has an internal diameter (ID) of 3.2 mm. IV line tubing mayform most of the blood passage through the blood circuit and have agenerally constant ID throughout the passage.

The pressure sensors may also have a blood passage that is contiguouswith the passages through the tubing and the ID of the passage in thesensors may be similar to the ID in the tubing. It is preferable thatthe entire blood passage through the blood circuit (from the withdrawalcatheter to the return catheter) have substantially the same diameter(with the possible exception of the filter) so that the blood flowvelocity is substantially uniform and constant through the circuit. Abenefit of a blood circuit having a uniform ID and substantiallycontinuous flow passages is that the blood tends to flow uniformlythrough the circuit, and does not form stagnant pools within the circuitwhere clotting may occur.

The roller blood pump 113 is rotated by a brushless DC motor housedwithin the console 106. The pump includes a rotating mechanism withorbiting rollers that are applied to a half-loop 119 in the bloodpassage tubing of the blood circuit. The orbital movement of the rollersapplied to tubing forces blood to move through the circuit. Thishalf-loop segment may have the same ID as does the other blood tubingportions of the blood circuit. The pump may displace approximately 1 ml(milliliter) of blood through the circuit for each full orbit of therollers. If the orbital speed of the pump is 60 RPM (revolutions perminute), then the blood circuit may withdraw 60 ml/min of blood, filterthe blood and return it to the patient. The speed of the blood pump 113may be adjusted by the controller to be fully occlusive until a pressurelimit of 15 psig (pounds per square inch above gravity) is reached. Atpressures greater than 15 psig, the pump rollers relieve because thespring force occluding the tube will be exceeded and the pump flow ratewill no longer be directly proportional to the motor velocity becausethe rollers will not be fully occlusive and will be relieving fluid.This safety feature ensures the pump is incapable of producing pressurethat could rupture the filter.

The withdrawal pressure sensor 109 is a flow-through type sensorsuitable for blood pressure measurements. It is preferable that thesensor have no bubble traps, separation diaphragms or other featuresincluded in the sensor that might cause stagnant blood flow and lead toinaccuracies in the pressure measurement. The withdrawal pressure sensoris designed to measure negative (suction) pressure down to −400 mm Hg.

All pressure measurements in the fluid extraction system are referencedto both atmospheric and the static head pressure offsets. The statichead pressure offsets arise because of the tubing placement and thepressure sensor height with respect to the patient connection. Thewithdrawal pressure signal is used by the microprocessor control systemto maintain the blood flow from the vein and limit the pressure.Typically, a peripheral vein can continuously supply between 60-200ml/min of blood. This assumption is supported by the clinical experiencewith plasma apheresis machines.

A pressure sensor 121 may be included in the circuit downstream of thepumps and upstream of the filter. Blood pressure in the post pump,pre-filter segment of the circuit is determined by the patient's venouspressure, the resistance to flow generated by the infusion catheter 103,resistance of hollow fibers in the filter assembly 108, and the flowresistance of the tubing in the circuit downstream of the blood pump113. At blood flows of 40 to 60 ml/min, in this embodiment, the pumppressure may be generally in a range of 300 to 500 mm Hg depending onthe blood flow, condition of the filter, blood viscosity and theconditions in the patient's vein.

The filter 108 is used to ultrafiltrate the blood and remove excessfluid from the blood. Whole blood enters the filter and passes through abundle of hollow filter fibers in a filter canister. There may beapproximately 700 to 900 hollow fibers in the bundle, and each fiber isa filter. In the filter canister, blood flows through an entrancechannel to the bundle of fibers and enters the hollow passage of eachfiber. Each individual fiber has approximately 0.2 mm internal diameter.The walls of the fibers are made of a porous material. The pores arepermeable to water and small solutes, but are impermeable to red bloodcells, proteins and other blood components that are larger than50,000-60,000 Daltons. Blood flows through the fibers tangential to thesurface of the fiber filter membrane. The shear rate resulting from theblood velocity is high enough such that the pores in the membrane areprotected from fouling by particles, allowing the filtrate to permeatethe fiber wall. Filtrate (ultrafiltrate) passes through the pores in thefiber membrane (when the ultrafiltrate pump is rotating), leaves thefiber bundle, and is collected in a filtrate space between the innerwall of the canister and outer walls of the fibers.

The membrane of the filter acts as a restrictor to ultrafiltrate flow.An ultrafiltrate pressure transducer (Puf) 111 is placed in theultrafiltrate line upstream of the ultrafiltrate roller pump 114. Theultrafiltrate pump 114 is rotated at the prescribed fluid extractionrate which controls the ultrafiltrate flow from the filter. Beforeentering the ultrafiltrate pump, the ultrafiltrate passes throughapproximately 20 cm of plastic tubing 120, the ultrafiltrate pressuretransducer (Puf) and the blood leak detector 118. The tubing is madefrom medical PVC of the kind used for IV lines and has internal diameter(ID) of 3.2 mm. The ultrafiltrate pump 114 is rotated by a brushless DCmotor under microprocessor control. The pump tubing segment (compressedby the rollers) has the same ID as the rest of the ultrafiltratecircuit.

The system may move through the filtrate line approximately 1 ml offiltrate for each full rotation of the pump. A pump speed of 1.66 RPMcorresponds to a filtrate flow of 1.66 ml/min, which corresponds to 100ml/hr of fluid extraction. The ultrafiltrate pump 114 is adjusted at thefactory to be fully occlusive until a pressure limit of 15 psig isreached. The rollers are mounted on compression springs and relievedwhen the force exerted by the fluid in the circuit exceeds the occlusivepressure of the pump rollers. The circuit may extract 100 to 500 ml/hrof ultrafiltrate for the clinical indication of fluid removal to relievefluid overload.

After the blood passes through the ultrafiltrate filter 108, it ispumped through a two meter infusion return tube 105 to the infusionneedle 103 where it is returned to the patient. The properties of thefilter 108 and the infusion needle 103 are selected to assure thedesired TMP (Trans Membrane Pressure) of 150 to 250 mm Hg at blood flowsof 40-60 ml/min where blood has hematocrit of 35 to 45% and atemperature of 34° C. to 37° C. The TMP is the pressure drop across themembrane surface and may be calculated from the pressure differencebetween the average filter pressure on the blood side and theultrafiltration pressure on the ultrafiltrate side of the membrane.Thus, TMP=((Inlet Filter Pressure+Outlet FilterPressure)/2)−Ultrafiltrate Pressure.

The blood leak detector 118 detects the presence of a ruptured/leakingfilter, or separation between the blood circuit and the ultrafiltratecircuit. In the presence of a leak, the ultrafiltrate fluid will nolonger be clear and transparent because the blood cells normallyrejected by the membrane will be allowed to pass. The blood leakdetector detects a drop in the transmissibility of the ultrafiltrateline to infrared light and declares the presence of a blood leak.

The pressure transducers Pw (withdrawal pressure sensor 109), Pin(infusion pressure sensor 110) and Puf (filtrate pressure sensor 111)produce pressure signals that indicate a relative pressure at eachsensor location. Prior to filtration treatment, the sensors are set upby determining appropriate pressure offsets. These offsets are used todetermine the static pressure in the blood circuit and ultrafiltratecircuit due to gravity. The offsets are determined with respect toatmospheric pressure when the blood circuit is filled with saline orblood, and the pumps are stopped. The offsets are measures of the staticpressure generated by the fluid column in each section, e.g.,withdrawal, return line and filtrate tube, of the circuit. Duringoperation of the system, the offsets are subtracted from the rawpressure signals generated by the sensors as blood flows through thecircuit. Subtracting the offsets from the raw pressure signals reducesthe sensitivity of the system to gravity and facilitates the accuratemeasurement of the pressure drops in the circuit due to circuitresistance in the presence of blood and ultrafiltrate flow. Absent theseoffsets, a false disconnect or occlusion alarm could be issued by themonitor CPU (714 in FIG. 7) because, for example, a static 30 cm columnof saline/blood will produce a 22 mm Hg pressure offset.

The pressure offset for a particular sensor is a function of the fluiddensity “p”, the height of the tube “h” and the earth's gravitationalconstant “g”:P _(offset) =ρ*g*h

-   -   where “ρ” and “g” are constants and, thus, pressure offsets are        a function of the sensor position. The pressure offsets are not        experienced by the patient. Proof of this is when a 3.2 mm ID        tube filled with water with its top end occluded (pipette) does        not allow the water to flow out. This means that the pressure at        the bottom of the tube is at 0 mm Hg gage. In order to normalize        the offset pressures, the offsets are measured at the start of        operation when the circuit is fully primed and before the blood        pump or ultrafiltrate pump are actuated. The measured offsets        are subtracted from all subsequent pressure measurements.        Therefore, the withdrawal pressure Pw, the infusion pressure Pin        and the ultrafiltrate pressure Puf are calculated as follows:        Pw=PwGage−PwOffset        Pin=PinGage−PinOffset        Puf=PufGage−PufOffset

PwOffset, PinOffset and PufOffset are measured when the circuit isprimed with fluid, and the blood and ultrafiltrate pumps are stopped.PwGage, PinGage and PufGage are measured in real time and are the raw,unadjusted gage pressure readings from the pressure transducers. Toincrease accuracy and to minimize errors due to noise, the offsets arechecked for stability and have to be stable within 2 mm Hg for 1 secondbefore an offset reading is accepted. The offset is averaged over 1second to further reduce sensitivity to noise.

FIG. 3 is a chart of pressure limits 300 in the blood circuit versus theblood flow rate 301 in the circuit. The chart shows graphicallyexemplary control algorithms for controlling pressure in the withdrawalline as a function of the actual blood flow. The blood flow rate isknown, and calculated from the known pump speed. An occlusion controlfunction 302 (PwOcc—Occlusion) provides a variable pressure limit vs.flow rate (sloped portion of PwOcc—Occlusion) for controlling theminimum pressure limit in the withdrawal line as a function of flowrate.

The maximum negative pressure (i.e., lowest suction level) in thewithdrawal line is limited by an algorithm 303 (disconnect—PwDisc) whichis used to sense when a disconnect occurs in the withdrawal line. Thewithdrawal line has a suction pressure (sub-atmospheric) pressure todraw blood from the peripheral artery. This suction pressure is shown asa negative pressure in mmHg in FIG. 3. If the actual suction pressurerises above a limit (PwDisc), then the controller may signal that adisconnect has occurred, especially if air is also detected in the bloodcircuit. The suction pressure in the withdrawal line is controlled to bebetween the occlusion and disconnect pressure limits 302, 303.

The maximum withdrawal resistance (PwOcc,—see the slope of line 302) fora given flow rate is described by the occlusion algorithm curve 302.This allowable occlusion pressure, PwOcc (401 in FIG. 4), increases asblood flow increases. This increase may be represented by a linear slopeof flow rate vs. pressure, that continues, until a maximum flow rate 304is reached. The occlusion algorithm curve is based on theoretical andempirical data with a blood Hct of 35% (maximum Hct expected in clinicaloperation), and the maximum expected resistance of the withdrawal needleand withdrawal blood circuit tube expected during normal operation whenmeasured at Pw.

The withdrawal pressure sensor signal (Pw) is also applied to determinewhether a disconnection has occurred in the withdrawal blood circuitbetween the withdrawal tubing 104 from the needle 102 or between theneedle and the patient's arm, or a rupture in the withdrawal tubing. Thecontrol algorithm for detecting a disconnection is represented by PwDisccurve 303. This curve 303 represents the minimum resistance of the 18Gage needle and withdrawal tubing, with a blood Hct of 25% (minimum Hctexpected in clinical operation), at a temperature of 37° C. The data togenerate this curve 303 may be obtained in vitro and later incorporatedin the controller software.

During the device operation the measured withdrawal pressure (Pw) isevaluated in real time, for example, every 10 milliseconds, by thecontroller. Measured Pw is compared to the point on the curve 303 thatcorresponds to the current blood flow rate. A disconnection is detectedwhen the pressure Pw at a given blood flow is greater than the pressuredescribed by curve 303, and if air is detected in the blood circuit. Ifthe withdrawal line becomes disconnected, the blood pump 113 willentrain air into the tubing due to the suction caused by the withdrawalpressure (Pw) when the blood pump is withdrawing blood. The pressuremeasured by the withdrawal pressure transducer Pw will increase (becomeless negative) in the presence of a disconnection because the resistanceof the withdrawal line will decrease.

FIG. 4 is a flow chart showing in mathematical terms the controlalgorithms shown in FIG. 3. The allowable occlusion pressure (PwOcc) 401is determined as a function of blood flow (QbMeas). The blood flow(QbMeas) may be determined by the controller, e.g., controller CPU,based on the rotational speed of the blood pump and the known volume ofblood that is pumped with each rotation of that pump, as is shown in theequation below:PwOcc=QbMeas*KwO+B

Where QbMeas is the measured blood flow, KwO is the withdrawal occlusioncontrol algorithm 302, e.g., a linear slope of flow vs. pressure, and Bis a pressure offset applied to the withdrawal occlusion, which offsetis described below.

The expression for PwOcc is a linear equation to describe. PwOcc mayalso be implemented as a look up table where a known QbMeas is enteredto obtain a value for PwOcc. In addition, the expression for PwOcc maybe a second order polynomial in the presence of turbulent flow. Theexpression for PwOcc to be chosen in a particular implementation will bebased upon the characteristics of the tube and the presence of laminaror turbulent flow.

The PwOcc signal may be filtered with a 0.2 Hz low pass filter to avoidfalse occlusion alarms, as indicated in the following sequential pair ofequations.PwOccFilt=PwOcc*(1−alpha)+PwOccFiltOld*alpha

-   -   Where alpha=exp(−t/Tau)    -   Where t=discrete real time sample interval in seconds and        The time constant Tau=1/(2*PI*Fc)

Where PI=3.1416 and Fc is equal to the cutoff frequency of the firstorder low pass filter in Hz.

Thus, for a 0.2 Hx filter, Tau=0.7957 therefore alpha=0.9875

Where PwOccFilt is the current calculated occlusion pressure limit forthe actual flow rate, after being filtered. PwOccFiltOld is the previouscalculated occlusion pressure, and “alpha” is a constant of the low passfilter. Thus, PwOccFiltOld=PwOccFilt, for each successive determinationof PwOccfilt.

Similar determinations are made for the calculated pressure limits forthe filtered withdrawal disconnect limit (PwDiscFilt), filtered infusiondisconnect limit (PinDiscFilt) and filtered infusion occlusion limit(PinOccFilt).

The PwDisc curve 303, shown in FIG. 3 is described in equation formbelow and shown in 401 of FIG. 4. The withdrawal disconnection pressure,PwDisc is calculated as a function (KwD) of blood flow, QbMeas which ismeasured blood flow calculated from the encoder pump speed signal.PwDisc=QbMeas*KwD+A

Where A is a pressure constant offset, and KwD represents the slope ofthe PwDisc curve 303. In addition, the PwDisc (withdrawal pressure limitfor disconnect) is filtered with a 0.2 Hz low pass filter to avoid falsedisconnect alarms, reference 401 in FIG. 4.

PwDisc is a linear equation to describe. PwDisc may also be implementedas a look up table where a known QbMeas is entered to obtain a value forQbMeas. In addition, the expression for PwDisc may be a second orderpolynomial in the presence of turbulent flow. The expression for PwDiscto be chosen in a particular implementation will be based upon thecharacteristics of the tube and the presence of laminar or turbulentflow.PwDiscFilt=PwDisc*(1−alpha)+PwDiscFiltOld*alphaPwDiscFiltOld=PwDiscFilt

Where alpha is a function of the filter.

The air detector 117 detects the presence of air when entrained. If thewithdrawal pressure (Pw) exceeds (is less negative than) the disconnectpressure (PwDisc) 303 and air is detected in the blood circuit by theair detector, then the controller declares a withdrawal disconnection,and the blood pump and the ultrafiltrate pump are immediately stopped.This logic function is expressed as:If (Pw>PwDiscFilt AND AirDetected=TRUE)

-   -   {then Declare a withdrawal disconnect}

The above logic function is a reliable detection of a withdrawal linedisconnection, while avoiding false alarms due to blood pressuremeasurements with blood pressure cuffs. For example, a false alarm couldbe generated when blood pressure cuffs are pressurized which causes anincreased venous pressure and in turn lower withdrawal pressure. Thelower withdrawal pressure caused by a blood pressure cuff might beinterpreted by the controller as a disconnection resulting in falsealarms, except for the logic requirement of air being detected.

The occlusion and disconnect pressure limits for the return (infusion)line are graphically shown in FIG. 6. These calculations are made in asimilar manner as described above for determining PwOccFilt. Theinfusion-occlusion pressure limit (PinOcc) 401 is calculated as afunction of blood flow (QbMeas) where QbMeas is actual blood flowcalculated from the pump speed feedback signal.

PinOcc=QbMeas*KwO+B, where KwO is the factor for converting (see FIG. 6,Occlusion line 601) the actual blood flow rate to a pressure limit. Theexpression for PinOcc is a linear equation to describe. PinOcc may alsobe implemented as a look up table where a known QbMeas is entered toobtain a value for PinOcc. In addition, the expression for PinOcc may bea second order polynomial in the presence of turbulent flow. Theexpression for PinOcc to be chosen in a particular implementation willbe based upon the characteristics of the tube and the presence oflaminar or turbulent flow.

PinOcc is filtered with a 0.2 Hz low pass filter to avoid falsedisconnect alarms.PinOccFilt=PinOcc*(1−alpha)+PinOccFiltOld*alphaPinOccFiltOld=PinOccFilt

FIG. 4 also shows the interaction of the control algorithms forwithdrawal occlusion (PwOccFilt) and the infusion occlusion(PinOccFilt). The control theory for having two control algorithmsapplicable to determining the proper flow rate is that only one of thecontrol algorithms will be applied to determine a target flow rate atany one time. To select which algorithm to use, the controller performsa logical “If-Then operation” 402 that determines whether the target isto be the withdrawal occlusion or infusion occlusion algorithms. Thecriteria for the If-Then operation is whether the infusion line isoccluded or not. If the infusion line is occluded, Pin is greater thanPinOccFilt; therefore, the Target is set to PinOccFilt.

In particular, the infusion occlusion algorithm (PinOccFilt) is thetarget (Target) and infusion pressure (Pin) is applied as a feedbacksignal (Ptxd), only when the infusion pressure (Pin) exceeds theocclusion limit for infusion pressure (PinOccFilt). Otherwise, theTarget is the occlusion withdrawal pressure limit (PwOccFilt) and thefeedback signal is the withdrawal pressure (Pw).

The If-Then (402) algorithm is set forth below in a logic statement (seealso the flow chart 402):

-   -   If (PinOccFilt<Pin)    -   {Then Target=−(PinOccFilt), and Ptxd=−(Pin)}    -   {Else Target=PwOccFilt and Ptxd=Pw}

A pressure controller (see FIG. 5 description) may be used to controlthe Ptxd measurement to the Target pressure. The Target pressure will beeither the PinOccFilt or PwOccFilt limit based upon the IF statementdescribed above.

FIG. 5 includes a functional diagram of a PIFF (Proportional IntegralFeed Forward) pressure controller 501 for the ultrafiltration apparatus100, and shows how the PIFF operates to control pressure and flow ofblood through the circuit. Controllers of the PIFF type are well knownin the field of “controls engineering”. The PIFF pressure controller 501controls the withdrawal pressure to the prescribed target pressure 502,which is the filtered withdrawal occlusion pressure limit (PwOccFilt),by adjusting the blood pump flow rate. The PIFF may alternatively use asa target the limit for infusion pressure (PinOccFilt). The targetpressure 502 limit is compared 503 to a corresponding actual pressure504, which is withdrawal pressure (Pw) if the target is PwOccFilt and isinfusion pressure (Pin) if the target is PinOccFilt. The actual pressureis applied as a feedback signal (Ptxd) in the PIFF. The logical compareoperation 503 generates a difference signal (Error) 505 that isprocessed by the PIFF.

The PIFF determines the appropriate total flow rate (Qtotal) based onthe difference signal 505, the current flow rate, the current rate ofincrease or decrease of the flow rate, and the flow rate limit. The PIFFevaluates the difference between the target pressure limit and actualpressure (feedback) with a proportional gain (Kp), an integral gain (Ki)and a feed forward term (FF). The proportional gain (Kp) represents thegain applied to current value of the error signal 505 to generate aproportional term (Pterm) 506, which is one component of the sum of thecurrent desired flow (Qtotal). The integral gain (Ki) is the othercomponent of Qtotal, and is a gain applied to the rate at which theerror signal varies with time (error dt). The product of the integralgain and the error dt (Iterm) is summed with the previous value of Itermto generate a current item value. The current Iterm value and Ptermvalue are summed, checked to ensure that the sum is within flow limits,and applied as the current desired total flow rate (Qtotal). Thisdesired flow rate (Qtotal) is then applied to control the blood pumpspeed, and, in turn, the actual flow rate through the blood circuit.

The gain of the PIFF pressure controller Kp and Ki have been chosen toensure stability when controlling with both withdrawal and infusionpressures. The same PIFF controller is used for limiting withdrawal andinfusion pressures. None of the controller terms are reset when thetargets and feedback transducers are switched. This ensures that thereare no discontinuities in blood flow and that transitions betweencontrol inputs are smooth and free from oscillation. Thus, when the PIFFpressure controller switches from controlling on withdrawal pressure topinfusion pressure the blood pump does not stop, it continues at avelocity dictated by the pressure control algorithm.

The proportional and integral gains (Kp and Ki) of the pressurecontroller are selected to ensure stability. Kp and Ki were chosen toensure that pressure overshoots are less than 30 mmHg, and that thepressure waveform when viewed on a data acquisition system was smoothand free of noise. In general Kp may be increased until the noise levelon the signal being controlled exceeds the desired level. Kp is thenreduced by 30%. Ki is chosen to ensure the steady state error iseliminated and that overshoot is minimized. Both the integral term andthe total flow output of the PIFF controller are limited to a maximum of60 ml/min, in this embodiment.

In addition, in this embodiment the flow limits for the integral termand total flow output may be increased linearly starting at a maximumrate of 20 ml/min (FF). When the PIFF controller is initially started,the integral term (Iterm) is set equal to the feed forward term (FF),which may be 20 ml/min. Thus, 40 seconds are required to increase theflow limit from an initial setting (20 ml/min) to the maximum value of60 ml/min. This 40 second flow increase period should be sufficient toallow the withdrawal vein to respond to increases in withdrawal flowrate. Limiting the rate of increase of the blood flow is needed becauseveins are reservoirs of blood and act as hydraulic capacitors. If a flowrate is increased too quickly, then a false high flow of blood can occurfor short periods of time because flow may be supplied by the elastanceof the vein (that determines compliance), and may not be truesustainable continuous flow much like an electrical capacitor willsupply short surges in current.

This PIFF pressure controller controls pressure in real time, and willimmediately reduce the pressure target if a reduction in flow occurs dueto an occlusion. The target pressure is reduced in order to comply withthe occlusion pressure limit, such as is shown in FIG. 3. Reducing thepressure target in the presence of an occlusion will lead to a furtherreduction in flow, which will result in a further reduction in thetarget pressure. This process limits the magnitude and duration ofnegative pressure excursions on the withdrawal side, and, therefore,exposure of the patient's vein to trauma. It also gives the withdrawal(or infusion) vein time to recover, and the patient's vein time toreestablish flow without declaring an occlusion.

When a withdrawal vein collapses, the blood pump will be stopped by thePIFF controller because the vein will have infinite resistance resultingin zero blood flow no matter to what pressure Pw is controlled. When theblood pump stops, the blood flow is reversed and blood is pumped intothe withdrawal vein in an attempt to open that vein. When the blood pumpis reversed, the withdrawal and infusion disconnect and occlusionalgorithms are still active protecting the patient from exposure to highpressures and disconnects. When the blood pump flow is reversed theocclusion limits and disconnect limits are inverted by multiplying bynegative 1. This allows the pump to reverse while still being controlledby maximum pressure limits.

-   -   If (Blood Pump is reversing)    -   {PwDiscFilt and PinDiscFilt and PwOccFilt and PwOccFilt are        inverted}

Two (2) ml of blood may be infused into the withdrawal line and into thewithdrawal peripheral vein by reversing the blood pump at 20 ml/min toensure that the vein is not collapsed. The blood pump is stopped for 2seconds and withdrawal is reinitiated. The controller issues an alarm torequest that the operator check vein access after three automaticattempts of reversing blood flow into the withdrawal line. The bloodcircuit has a total volume of approximately 60 ml. The blood pump islimited to reversing a total volume of five ml thereby minimizing thepossibility of infusing the patient with air.

The PIFF applies a maximum withdrawal flow rate (maxQb) and a minimumwithdrawal flow rate (minQb). These flow rate boundaries are applied aslimits to both the integration term (Item) and the sum of the flowoutputs (Qtotal). The maximum withdrawal rate is limited to, e.g., 60ml/min, to avoid excessive withdrawal flows that might collapse the veinin certain patient populations. The minimum flow rate (minQb) is appliedto the output flow to ensure that the pump does not retract at a flowrate higher than −60 ml/min. In addition, if the actual flow rate (Qb)drops below a predetermined rate for a certain period of time, e.g., 20ml/min for 10 seconds, both the blood pump and ultrafiltrate pump arestopped.

The ultrafiltrate pump is stopped when the blood pump flow is less than40 ml/min. If the ultrafiltrate pump is not stopped, blood can becondensed too much inside the fibers and the fibers will clot. A minimumshear rate of 1000 sec-1 in blood is desirable if fouling is to beavoided. This shear rate occurs at 40 ml/min in the 0.2 mm diameterfilter fibers. The shear rate decreases as the flow rate decreases.Fouling may be due to a buildup of a protein layer on the membranesurface and results in an increase in trans-membrane resistance that canultimately stop ultrafiltration flow if allowed to continue. By ensuringthat no ultrafiltration flow occurs when a low blood shear rate ispresent, the likelihood of fouling is decreased.

When the system starts blood flow, the ultrafiltration pump is held inposition and does not begin rotation until the measured and set bloodflow are greater than 40 ml/min. If the set or measured blood flow dropsbelow 40 ml/min, the ultrafiltrate pump is immediately halted. Thisprevents clogging and fouling. Once blood flow is re-established and isgreater than 40 ml/min, the ultrafiltrate pump is restarted at the userdefined ultrafiltration rate. When the blood pump is halted theultrafiltrate pump is stopped first, followed by the blood pump ensuringthat the filter does not become clogged because the ultrafiltrate pumpwas slower at stopping, resulting in ultrafiltrate being entrained whileblood flow has ceased. This can be implemented with a 20 milliseconddelay between halt commands.

FIG. 6 graphically shows the control algorithms for the blood infusionpressure. The patient may be exposed to excessively high pressures if anocclusion occurs in the infusion vein. Control algorithms are used forcontrolling the maximum allowable infusion pressure. These algorithmsare similar in concept to those for controlling the maximum allowablewithdrawal pressure. The maximum occlusion pressure algorithm 601 is apositive relationship between the flow rate (Qb) and infusion pressure(Pin) as measured by the pressure sensor in the return line 110. Asshown in the algorithm curve 601, as the flow rate increases theacceptable infusion pressure similarly increases, up to a maximum limit.

The algorithm curve 601 provides the maximum infusion pressure, Pin, forgiven blood flow. The maximum allowable positive pressure PinOccincreases as blood flow Qb increases. This curve was generated fromtheoretical and empirical data with a blood Hct of 45% (maximum expectedclinically), and is based on the maximum resistance of the infusiontubing 105 and the infusion needle 103. The curve may vary withdifferent embodiments, depending on other data used to generate such acurve.

FIG. 7 illustrates the electrical architecture of the ultrafiltratesystem 700 (100 in FIG. 1), showing the various signal inputs andactuator outputs to the controller. The user-operator inputs the desiredultrafiltrate extraction rate into the controller by pressing buttons ona membrane interface keypad 709 on the controller. These settings mayinclude the maximum flow rate of blood through the system, maximum timefor running the circuit to filter the blood, the maximum ultrafiltraterate and the maximum ultrafiltrate volume. The settings input by theuser are stored in a memory 715 (mem.), and read and displayed by thecontroller CPU 705 (central processing unit, e.g., microprocessor ormicro-controller) on the display 710.

The controller CPU regulates the pump speeds by commanding a motorcontroller 702 to set the rotational speed of the blood pump 113 to acertain speed specified by the controller CPU. Similarly, the motorcontroller adjusts the speed of the ultrafiltrate pump 111 in responseto commands from the controller CPU and to provide a particular filtrateflow velocity specified by the controller CPU. Feedback signals from thepressure transducer sensors 711 are converted from analog voltage levelsto digital signals in an A/D converter 716. The digital pressure signalsare provided to the controller CPU as feedback signals and compared tothe intended pressure levels determined by the CPU. In addition, thedigital pressure signals may be displayed by the monitor CPU 714.

The motor controller 702 controls the velocity, rotational speed of theblood and filtrate pump motors 703, 704. Encoders 707, 706 mounted tothe rotational shaft of each of the motors as feedback providequadrature signals, e.g., a pair of identical cyclical digital signals,but 90° out-of-phase with one another. These signal pairs are fed to aquadrature counter within the motor controller 702 to give bothdirection and position. The direction is determined by the signal leadof the quadrature signals. The position of the motor is determined bythe accumulation of pulse edges. Actual motor velocity is computed bythe motor controller as the rate of change of position. The controllercalculates a position trajectory that dictates where the motor must beat a given time and the difference between the actual position and thedesired position is used as feedback for the motor controller. The motorcontroller then modulates the percentage of the on time of the PWMsignal sent to the one-half 718 bridge circuit to minimize the error. Aseparate quadrature counter 717 is independently read by the ControllerCPU to ensure that the Motor Controller is correctly controlling thevelocity of the motor. This is achieved by differentiating the change inposition of the motor over time.

The monitoring CPU 714 provides a safety check that independentlymonitors each of the critical signals, including signals indicative ofblood leaks, pressures in blood circuit, weight of filtrate bag, motorcurrents, air in blood line detector and motor speed/position. Themonitoring CPU has stored in its memory safety and alarm levels forvarious operating conditions of the ultrafiltrate system. By comparingthese allowable preset levels to the real-time operating signals, themonitoring CPU can determine whether a safety alarm should be issued,and has the ability to independently stop both motors and reset themotor controller and controller CPU if necessary.

Peripheral vein access presents unique problems that make it difficultfor a blood withdrawal controller to maintain constant flow and to notcreate hazards for the patient. For example, a patient may stand upduring treatment and thereby increase the static pressure head height onthe infusion side of the blood circuit. As the patient rises eachcentimeter (cm), the measured pressure in the extracorporeal circuitincreases by 0.73 mm Hg. This static pressure rise (or fall) will bedetected by pressure sensors in the withdrawal tube. The controlleradjusts the blood flow rate through the extracorporeal circuit toaccommodate for such pressure changes and ensures that the changes donot violate the pressure limits set in the controller.

In addition, the patient may bend their arm during treatment, therebyreducing the blood flow to the withdrawal vein. As the flow through thewithdrawal catheter decreases, the controller reduces pump speed toreduce the withdrawal pressure level. Moreover, the blood infusion sideof the blood circulation circuit may involve similar pressure variances.These infusion side pressure changes are also monitored by thecontroller which may adjust the pump flow rate to accommodate suchchanges.

In some cases, blood flow can be temporarily impeded by the collapse ofthe withdrawal vein caused by the patient motion. In other cases thewithdrawal vein of the patient may not be sufficient to supply themaximum desired flow of 60 ml/min. The software algorithms enable thecontroller to adjust the withdrawal flow rate of blood to prevent orrecover from the collapse of the vein and reestablish the blood flowbased on the signal from the withdrawal pressure sensor.

A similar risk of disconnection exists when returning the patient'sblood. The infusion needle or the infusion tube between the outlet ofthe infusion pressure transducer (Pin) and needle may becomedisconnected during operation. A similar disconnection algorithm (asdescribed for the withdrawal side) is used for detecting the presence ofdisconnections on the infusion side. In this case an air detector is notused because nursing staff do not place pressure cuffs on the arm beinginfused because of risk of extravasation. Since the blood is beinginfused the pressures measured by the infusion pressure transducer Pinare positive. The magnitude of Pin will decrease in the presence of adisconnection due to a decrease in the resistance of the infusion line.

A disconnection is detected when the pressure Pin at a given blood flowis less than the pressure described by curve 602 (FIG. 6) for the samesaid blood flow. The minimum resistance of the 18 Gage needle andwithdrawal tubing, with a blood Hct of 35%, at a temperature of 37° C.are represented by the curve 602. The curve 602, shown in FIG. 6 isdescribed in equation form in 401 (FIG. 4). The infusion disconnectionpressure, PinDisc 401 is calculated as a function of blood flow, QbMeaswhere QbMeas, is actual blood flow calculated from the encoder velocity.PinDisc=QbMeas*KinD+C

PinDisc is filtered with a 0.2 Hz low pass filter to avoid falsedisconnection alarms, reference 401 FIG. 4.0. The present embodimentuses a linear equation to describe PinDisc, but this equation could alsobe implemented as a look-up table or a second order polynomial in thepresence of turbulent flow. The implementation chosen will be based uponthe characteristics of the tube and the presence of laminar or turbulentflow.PinDiscFilt=PinDisc*(1−alpha)+PinDiscFiltOld*alphaPinDiscFiltOld=PinDiscFilt

If Pin is less than PinDiscFilt for 2 seconds consecutively, an infusiondisconnect is declared and the blood pump and ultrafiltrate pump areimmediately stopped.

-   -   If (Pin>PinDiscFilt)    -   {Then Increment Infusion Disconnect Timer}    -   {else Reset Infusion Disconnect Timer}    -   If (Reset Infusion Disconnect Timer=2 seconds)    -   {then Declare Infusion Disconnection}

The withdrawal and infusion occlusion detection algorithms use similarmethods of detection. Only the specific coefficients describing themaximum and minimum allowable resistances are different.

The purpose of the withdrawal occlusion algorithm is to limit thepressure in the withdrawal vein from becoming negative. A negativepressure in the withdrawal vein will cause it to collapse. The venouspressure is normally 15 mm Hg and it will remain positive as long as theflow in the vein is greater than the flow extracted by the blood pump.

If the resistance of the withdrawal needle and blood circuit tube areknown, the withdrawal flow may be controlled by targeting a specificwithdrawal pressure as a function of desired flow and known resistance.For example, assume that the resistance of the withdrawal needle toblood flow is R and that R equals −1 mm Hg/ml/min. In order for 60ml/min of blood to flow through the needle, a pressure drop of 60 mm Hgis required. The pressure may be either positive, pushing blood throughthe needle or negative, withdrawing blood through the needle. On thewithdrawal side of the needle, if a pressure of −60 mm Hg is targeted ablood flow of 60 ml/min will result.

If the flow controller is designed to be based upon resistance, thepressure target required to give the desired flow rate Q would be R*Q.Thus, if a flow of 40 ml/min were required, a pressure of −40 mm Hgwould be required as the pressure target. Since the system knowswithdrawal flow based upon encoder velocity and is measuring withdrawalpressure, the system is able to measure the actual withdrawal resistanceof the needle in real time.

If a maximum resistance limit is placed on the withdrawal needle of −1.1mm Hg/ml/min, the pressure controller will stop withdrawing flow in thepresence of an occlusion. Occlusion can be in the circuit or caused bythe vein collapse. The resistance limit is implemented as a maximumpressure allowed for a given flow. Thus, for a resistance limit of −1.1mm Hg, if the flow drops to 30 ml/min when the current withdrawalpressure is −60 mm Hg in the presence of an occlusion, the maximumpressure allowed is 30 ml/min*−1.1 mm Hg/ml/min=33 mm Hg. This meansthat the occlusion resistance is −60/30=−2 mm Hg/ml/min. If theocclusion persists when the withdrawal pressure drops to −33 mm Hg, theflow will be reduced to 16.5 ml/min. This will result in a new pressuretarget of −18.15 mm Hg and so on until the flow stops.

The actual pressure target to deliver the desired flow is difficult toascertain in advance because of the myriad of variables which effectresistance, blood Hct, needle size within and length within the expectedtolerance levels, etc. Instead, the pressure controller targets themaximum resistance allowed, and the flow is limited by the maximum flowoutput allowed by the pressure controller.

A goal of the control algorithm is to ensure that the pressure at thewithdrawal vein never falls below 0 mmHg where vein collapse couldoccur, or that the infusion pressure exceeds a value that could causeextravasation. If the critical pressure-flow curve is generated at theworst case conditions (highest blood viscosity), the controller willensure that the pressure in the vein is always above the collapse levelor below the extravasation level.

In the fluid path configuration of the blood circuit shown in FIG. 2,there is no pressure transducer at the blood pump outlet and entry tothe filter. If a pressure transducer were present, then its signal couldalso be fed to the PIFF pressure controller using the same pressurelimitation methods already described. A specific disconnect andocclusion algorithm could be defined to describe the maximum and minimumflow vs. pressure curves based upon the filter and infusion limbresistance. Alternatively, a limit on the current consumed by the motorcan be used to detect the presence of an occlusion in the infusion andfilter limb. High pressures at the filter inlet will not be detected bythe infusion pressure transducer, (Pin), because it is downstream ofthis potential occlusion site. A disconnection at the inlet to thefilter will be detected by the infusion disconnection algorithm, becauseif the filter becomes disconnected there will be no flow present in theinfusion limb and this will be interpreted by the infusion disconnectionalgorithm as an infusion disconnection.

The blood pump uses a direct drive brushless DC motor. This design waschosen for long life and efficiency. Using this approach has the addedbenefit of being able to measure pump torque directly. With DC motorsthe current consumed is a function of motor velocity and torque. Thecurrent consumed by the motor may be measured directly with a seriesresistor as indicated by 701, FIG. 7. This current is a function of theload torque and back EMF generated by the motor as a function of itsspeed and voltage constant. Thus:T _(motor) =T _(pump) +T _(tube)  Equation 1

Where T_(motor) is the torque required to drive the motor, T_(pump) isthe torque required to overcome the pressure in the tubing, T_(tube) isthe torque required to compress the tube.T _(motor)=(I _(motor)−(RPM*KV)/R _(motor))*KT  Equation 2T _(motor)=(I _(motor) −IEMF)*KT  Equation 3

Where T_(motor)=Torque oz-in, RPM=revs per min of motor, I_(motor) isthe current consumed by the motor, KV is the voltage constant of themotor Volts/rpm, R_(motor)=electrical resistance of motor in ohms andKT=the torque constant of the motor in oz-in/amp. KV and KT areconstants defined by the motor manufacturer. The RPM of the motor may becalculated from the change in position of the motor encoder. Thus, bymeasuring the current consumed by the motor, the torque produced by themotor can be calculated if the speed and physical parameters of themotor are known.

The torque consumed by the motor is a function of withdrawal pressure,the blood pump outlet pressure and the tubing compressibility. Thetorque required to compress the blood circuit tubing is relativelyconstant and is independent of the blood flow rate. A good indication ofthe blood pump outlet pressure may be calculated as a function of thecurrent consumed by the blood pump motor and may be used to indicate thepresence of a severe occlusion.

The pump Pressure Pp may be expressed as:T _(pump) =T _(motor) −T _(tube)  Equation 4Pp=T _(pump) *K  Equation 5Where K=A/RPp=(T _(motor) −T _(tube))*K  Equation 6

Where Pp is the blood pump outlet pressure, T_(motor) is the totaltorque output by the motor, T_(tube) is the torque required to squeezethe blood circuit tube K and is a conversion constant from torque topressure. K is calculated by dividing the cross-sectional area of theblood circuit tube internal diameter 3.2 mm by the radius R of theperistaltic blood pump.

Since K and T_(tube) are constants for the system and the blood flow hasa range of 40 to 60 ml/min also making the back EMF currentapproximately constant. The motor current may be used directly withoutany manipulation to determine the presence of an occlusion as analternative to calculating Pp. Thus, when the current limit of the bloodpump exceeds, for example 3 amps, both the blood pump and theultrafiltrate pump are stopped.

FIG. 8 illustrates the operation of a prototype apparatus constructedaccording to the current embodiment illustrated by FIGS. 1 to 7 underthe conditions of a partial and temporary occlusion of the withdrawalvein. The data depicted in the graph 800 was collected in real time,every 0.1 second, during treatment of a patient. Blood was withdrawnfrom the left arm and infused into the right arm in different veins ofthe patient using similar 18 Gage needles. A short segment of data,i.e., 40 seconds long, is plotted in FIG. 8 for the following traces:blood flow in the extracorporeal circuit 804, infusion pressureocclusion limit 801 calculated by CPU 705, infusion pressure 809,calculated withdrawal pressure limit 803 and measured withdrawalpressure 802. Blood flow 804 is plotted on the secondary Y-axis 805scaled in mL/min. All pressures and pressure limits are plotted on theprimary Y-axis 806 scaled in mmHg. All traces are plotted in real timeon the X-axis 807 scaled in seconds.

In the beginning, between time marks of 700 and 715 seconds, there is noobstruction in either infusion or withdrawal lines. Blood flow 804 isset by the control algorithm to the maximum flow limit of 55 mL/min.Infusion pressure 809 is approximately 150 to 200 mmHg and oscillateswith the pulsations generated by the pump. Infusion occlusion limit 801is calculated based on the measured blood flow of 55 mmHg and is equalto 340 mmHg. Similarly, the withdrawal pressure 802 oscillates between−100 and −150 mmHg safely above the dynamically calculated withdrawalocclusion limit 803 equal to approximately −390 mmHg.

At approximately 715 seconds, a sudden period of partial occlusion 808occurred. The occlusion is partial because it did not totally stop theblood flow 804, but rather resulted in its significant reduction from 55mL/min to between 25 and 44 mL/min. The most probable cause of thispartial occlusion is that as the patient moved during blood withdrawal.The partial occlusion occurred at the intake opening of the bloodwithdrawal needle. Slower reduction in flow can also occur due to aslowing in the metabolic requirements of the patient because of a lackof physical activity. Squeezing a patient's arm occasionally willincrease blood flow to the arm, which results in a sudden sharp decrease810 of the withdrawal pressure 802 from −150 mmHg to −390 mmHg at theocclusion detection event 811. The detection occurred when thewithdrawal pressure 810 reached the withdrawal limit 803. The controllerCPU responded by switching from the maximum flow control to theocclusion limit control for the duration of the partial occlusion 808.Flow control value was dynamically calculated from the occlusionpressure limit 803. That resulted in the overall reduction of blood flowto 25 to 45 mL/min following changing conditions in the circuit.

FIG. 8 illustrates the occlusion of the withdrawal line only. Althoughthe infusion occlusion limit 801 is reduced in proportion to blood flow804 during the occlusion period 808, the infusion line is neveroccluded. This can be determined by observing the occlusion pressure 809always below the occlusion limit 801 by a significant margin, while thewithdrawal occlusion limit 803 and the withdrawal pressure 802 interceptand are virtually equal during the period 808 because the PIFFcontroller is using the withdrawal occlusion limit 803 as a target.

The rapid response of the control algorithm is illustrated by immediateadjustment of flow in response to pressure change in the circuit. Thisresponse is possible due to: (a) servo controlled blood pump equippedwith a sophisticated local DSP (digital signal processing) controllerwith high bandwidth, and (b) extremely low compliance of the blood path.The effectiveness of controls is illustrated by the return of the systemto the steady state after the occlusion and or flow reductiondisappeared at the point 812. Blood flow was never interrupted, alarmand operator intervention were avoided and the partial occlusion wasprevented from escalation into a total occlusion (collapse of the vein)that would have occurred if not for the responsive control based on thewithdrawal pressure.

If the system response was not this fast, it is likely that the pumpwould have continued for some time at the high flow of 55 mL/min. Thishigh flow would have rapidly resulted in total emptying of the vein andcaused a much more severe total occlusion. The failure to quicklyrecover from the total occlusion can result in the treatment time loss,potential alarms emitted from the extracorporeal system, and a potentialneed to stop treatment altogether, and/or undesired user intervention.Since user intervention can take considerable time, the blood will bestagnant in the circuit for a while. Stagnant blood can be expected toclot over several minutes and make the expensive circuit unusable forfurther treatment.

FIG. 9 illustrates a total occlusion of the blood withdrawal vein accessin a different patient, but using the same apparatus as used to obtainthe data shown in FIG. 8. Traces on the graph 900 are similar to thoseon the graph 800. The primary Y-axis (months) and secondary Y-axis(mL/min) correspond to pressure and flow, respectively, in the bloodcircuit. The X-axis is time in seconds. As in FIG. 8 the system is insteady state at the beginning of the graph. The blood flow 804 iscontrolled by the maximum flow algorithm and is equal to 66 mL/min Thewithdrawal pressure 802 is at average of −250 mmHg and safely above theocclusion limit 803 at −400 mmHg until the occlusion event 901. Infusionpressure 809 is at average of 190 mmHg and way below the infusionocclusion limit 801 that is equal to 400 mmHg.

As depicted in FIG. 9, the occlusion of the withdrawal access is abruptand total. The withdrawal vein has likely collapsed due to the vacuumgenerated by the needle or the needle opening could have sucked in thewall of the vein. The withdrawal vein is completely closed. Similar tothe partial occlusion illustrated by FIG. 8, the rapid reduction of theblood flow 804 by the control system in response to the decreasing (morenegative) withdrawal pressure 802 prevented escalation of the occlusion,but resulted in crossing of the occlusion limit 803 into positive valuesat the point 902. Simultaneously the blood flow 804 dropped to zero andsequentially became negative (reversed direction) for a short durationof time 903. The control system allowed reversed flow continued for 1second at 10 mL/min as programmed into an algorithm. This resulted inpossible re-infusion of 0.16 mL of blood back into the withdrawal vein.These parameters were set for the experiment and may not reflect anoptimal combination. The objective of this maneuver is to release thevein wall if it was sucked against the needle orifice. It alsofacilitated the refilling of the vein if it was collapsed.

During the short period of time when the blood flow in the circuit wasreversed, occlusion limits and algorithms in both infusion andwithdrawal limbs of the circuit remained active. The polarity of thelimits was reversed in response to the reversed direction of flow andcorresponding pressure gradients.

The success of the maneuver is illustrated by the following recoveryfrom total occlusion. At the point 904 signifying the end of allowedflow reversal, the withdrawal occlusion limit 803 became negative andthe infusion occlusion limit 801 became positive again. The blood pumpstarted the flow increase ramp shown between points 904 and 905. Thegradual ramp at a maximum allowed rate is included in the totalocclusion recovery algorithm to prevent immediate re-occlusion and toallow the withdrawal vein to refill with blood.

For the example illustrated by FIG. 9, the most likely cause of theocclusion was suction of the blood vessel wall to the withdrawal needleintake opening The occlusion onset was rapid and the conditiondisappeared completely after the short reversal of flow that allowed thevessel to re-inflate. It can be observed that while the withdrawalocclusion ramp 907 followed the blood flow ramp 905, the measuredwithdrawal pressure 906 did not anymore intercept it. In fact, by thetime the steady-state condition was restored, the withdrawal pressure910 was at approximately −160 mmHg. Prior to occlusion the withdrawalpressure level 802 was approximately −200 mmHg. Thus, the withdrawalconditions have improved as a result of the total occlusion maneuver.

The preferred embodiment of the invention now known to the invention hasbeen fully described here in sufficient detail such that one of ordinaryskill in the art is able to make and use the invention using no morethan routine experimentation. The embodiments disclosed herein are notall of the possible embodiments of the invention. Other embodiments ofthe invention that are within the sprite and scope of the claims arealso covered by this patent.

What is claimed is:
 1. A method for controlling blood flow in a closedloop extracorporeal blood circulation system where blood is withdrawnand returned into a blood vessel in the same body in the process oftreatment, the method comprising: a. withdrawing blood from a bloodvessel of the patient at a controlled flow rate; b. measuring awithdrawal pressure of the withdrawn blood; c. infusing the withdrawnblood into the patient; d. measuring the infusion pressure of the blood;e. comparing the withdrawal pressure to a withdrawal pressure target,and comparing the infusion pressure to an infusion pressure target; f.adjusting the flow rate to reduce a difference between the withdrawalpressure and a withdrawal pressure target, in response to the infusionpressure being less than an infusion pressure target, and g. adjustingthe flow rate to reduce a difference between the infusion pressure andan infusion pressure target, in response to the infusion pressure beinggreater than the infusion pressure target.
 2. A method as in claim 1wherein step (g) includes applying a difference between the infusionpressure and the infusion pressure target as feedback to adjust the flowrate of the blood being withdrawn.
 3. A method as in claim 1 wherein theblood is withdrawn through a withdrawal needle and infused through aninfusion needle.
 4. A method as in claim 1 wherein the blood iswithdrawn through a needle and infused through said needle.
 5. A methodas in 1 wherein blood is withdrawn from and infused into a peripheralvein of a patient.